Poly(ADP-ribose) is synthesized at nicks and breaks in double-stranded DNA. We shall determine how the responsible enzyme interacts with the DNA, how the interaction results in poly(ADP-ribose) formation, by which direction the chains elongate and whether free chains precede or are derived from protein-bound chains. We shall examine the poly(ADP-ribosylation) of histones in natural nucleosomes and in nucleosomes reconstituted upon specific fragments of DNA and located at different distances from the fragment termini. We shall isolate tissue culture cells containing variant poly(ADP-ribose) polymerases in order to further examine the proposed roles of poly(ADP-ribose) in DNA repair.